Background Coordinated regulation of nutrient and inflammatory responses by six transmembrane epithelial antigen of prostate 4 (STEAP4) was essential for metabolic homeostasis. STEAP4 expression in human white adipose tissuewas associated with obesity. This study aimed to evaluate association between STEAP4 genetic polymorphisms and obesity in Uygur Chinese general population.Methods The functional regions of STEAP4 gene were sequenced in 96 Uygur with obesity (body mass index (BMI)>30 kg/m2). Representative variations were selected according to the function and linkage disequilibrium and genotyped in 1507 obesity (BMI ≥25 kg/m2) and 825 non-obesity control (BMI ＜25 kg/m2), all of whom were selected from epidemiology study of obesity-related diseases during January to February 2007 among Uygur population in Hetian area of Xinjiang Uygur Autonomous Region.Results Fourteen novel and 6 known single nucleotide polymorphism (SNPs), including 2 nonsynonymous SNPs (nsSNPs), in the STEAP4 gene were identified. Of the 3 representative SNPs, the nsSNP rs1981529 (Gly75Asp, 224A/G)was significantly associated with obesity phenotype (additive P/Pc=0.001/0.006, dominant P/Pc=0.003/0.018, odds ratio (OR) and 95％ confidence interval (CI) adjusted for age, gender and drinking 0.755 (0.641-0.890) and 0.750(0.621-0.907), respectively). By the multiple linear regression analysis, the quantitative phenotypes of BMI (P/Pc=0.002/0.004) and waist circumference (P/Pc=0.004/0.008) were found to be significantly associated with the genotypes of rs1981529 (Gly75Asp, 224A/G) in Uygur general population, and effect size (beta value) of one allele G of rs1981529 (Gly75Asp, 224A/G) was-0.553 kg/m2 for BMI and -1.311 cm for waist circumference after controlling age,gender and drinking factors.Conclusions The present study shows an association of the common variation rs1981529 (Gly75Asp, 224A/G) in the STEAP4 gene with obesity in Uygur general population. Further studies should replicate the results using larger populations.